Abstract:Objective To study the effect and mechanism of miR-140-3p in attenuating interleukin-1 β(IL-1β) induced chondrocyte injury via targeting apoptosis gene Bcl-2 associated X protein (BAX).Methods Rat osteoarticular chondrocytes ATDC5 were cultured and the expression levels of miR-140-3p and BAX were detected after the treatment of different concentration of IL-1β(0,1,5,10ng/mL).Then cells were treated with 10ng/mL IL-1β,at the same time,negative control (NC) miR or miR-140-3p was transfected,NC adenovirus or BAX adenovirus was infected.The cell survival rate,apoptosis rate,miR-140-3p,Bax and cleaved caspase-3 expression levels were detected.The dual luciferase reporter gene experiment was used to verify the effect of miR-140-3p targeting BAX.Results The expression of miR-140-3p decreased and BAX increased in ATDC5 cells treated with different concentrations of IL-1 β(P<0.05).The survival rate and the expression level of miR-NC+IL-1β group were lower than those of miR-NC group,while the apoptosis rate and the expression levels of BAX and Cleaved caspase-3 were higher than those of miR-NC group(P<0.05).The survival rate and the expression level of miR-140+IL-1β group were higher than those of miR-NC+IL-1β group,while the apoptosis rate and the expression levels of BAX and Cleaved caspase-3 were lower than those of miR-NC+IL-1β group(P<0.05).The survival rate of miR-140+Ad-BAX+IL-1β group was lower than that of miR-140+Ad-NC+IL-1β group,while the apoptosis rate and the expression levels of BAX and Cleaved caspase-3 were higher than those of miR-140+Ad-NC+IL-1β group(P<0.05).Conclusion IL-1β plays a protective role in IL-1β induced chondrocyte injury model,and targeting BAX and inhibiting apoptosis are related molecular mechanisms.
[1]Li SH,Wu QF.MicroRNAs target on cartilage extracellular matrix degradation of knee osteoarthritis[J].Eur Rev Med Pharmacol Sci,2021,25(3):1185-1197.
[2]Swingler TE,Niu L,Smith P,et al.The function of microRNAs in cartilage and osteoarthritis[J].Clin Exp Rheumatol,2019,120(5):40-47.
[3]Al-Modawi RN,Brinchmann JE,Karlsen TA.Multi-pathway protective effects of micrornas on human chondrocytes in an in vitro model of osteoarthritis[J].Mol Ther Nucleic Acids,2019,6(17):776-790.
[4]殷春明,潘晓华.膝骨关节炎患者关节液中miR-140-3p表达可反映骨关节炎进程[J].中国组织工程研究,2016,20(35):5277-5283.
[5]Wang Z,Zhang S,Zhao Y,et al.MicroRNA140-3p alleviates intervertebral disc degeneration via KLF5/N-cadherin/MDM2/Slug axis[J].RNA Biol,18(12):2247-2260.
[6]Tan C,Zhang J,Chen W,et al.Inflammatory cytokines via up-regulation of aquaporins deteriorated the pathogenesis of early osteoarthritis[J].PLoS One,2019,14(8):e0220846.
[7]王新军,袁银鹏,王越,等.软骨细胞凋亡引发骨关节炎的机制研究进展[J].山东医药,2020,60(2):109-112.
[8]阿布都艾尼·热吾提,周文正,车立新,等.LINC00052靶向miR-145发挥对TNF-α诱导人关节软骨细胞损伤的保护作用[J].实用骨科杂志,2021,27(9):804-810.
[9]Chao Y,Zhang L,Zhang X,et al.Expression of MiR-140 and MiR-199 in synovia and its correlation with the progression of knee osteoarthritis[J].Med SciMonit,2020,20(26):e918174.
[10]Sun T,Xue JB,Zhou YL,et al.Myricitrin regulates proliferation,apoptosis and inflammation of chondrocytes treated with IL-1β[J].Cell Mol Biol (Noisy-le-grand),2020,66(1):65-69.
[11]Jia Y,He W,Zhang H,et al.Morusin ameliorates IL-1βinduced chondrocyte inflammation and osteoarthritis via NF-κB signal pathway[J].Drug Des DevelTher,2020,26(14):1227-1240.
[12]Cao J,Zhang Y,Wang T,et al.Endoplasmic reticulum stress is involved in baicalin protection on chondrocytes from patients with osteoarthritis[J].Dose Response,2018,16(4):1559325818810636.
[13]Kourtis A,Adamopoulos PG,Papalois A,et al.Quantitative analysis and study of the mRNA expression levels of apoptotic genes BCL-2,BAX and BCL-2L-12- in the articular cartilage of an animal model of osteoarthritis[J].Ann Transl Med,2018,6(12):243.
[14]Miao G,Zang X,Hou H,et al.Bax targeted by miR29a regulates chondrocyte apoptosis in osteoarthritis[J].Biomed Res Int,2019,12(2019):1434538.
[15]He B,Wu F,Li X,et al.Mitochondrial dependent pathway is involved in the protective effects of carboxymethylated chitosan on nitric oxide-induced apoptosis in chondrocytes[J].BMC Complement Med Ther,2020,20(1):23.
[16]Zhuang C,Ni S,Yang ZC,et al.Oxidative stress induces chondrocyte apoptosis through caspase-dependent and caspase-independent mitochondrial pathways and the antioxidant mechanism of angelica sinensis polysaccharide[J].Oxid Med Cell Longev,2020,7(2020):3240820.